In-vitro diagnostic agents use, for instance, blood, urine, saliva and tissue of patients to find types of diseases and causes thereof, while minimizing the effect upon a human body, and thus play an important role in early diagnosis and early treatment. The in-vitro diagnostic agents are applied to various diagnostic uses, and are helpfully used in pregnancy diagnosis and primary screening tests such as a screening test for colon cancer based on determination of fecal occult blood. As the in-vitro diagnostic agent as mentioned above, gold colloid having an antibody for detecting a target antigen for diagnosis bound on the surface thereof has been known.
To effectively use the in-vitro diagnostic agent, it is required to improve the sensitivity and thereby maintain reliability of diagnosis. To realize this, it is necessary to use gold colloid having a particle size suitable for various uses as mentioned above. For example, since extremely high sensitivity is required to the in-vitro diagnostic agent for pregnancy, gold colloid is desired to have a uniform particle size of 40 nm and a sharp particle size distribution.
When the antibodies for use in the in-vitro diagnostic agent are directly bound onto gold colloid, they are sometimes randomly coordinated. For this reason, a protein or an organic substance called a linker is sometimes bound in advance. To bind a desired number of linkers onto gold colloid at regular intervals, the gold colloid is required to have a uniform size and a virtually perfect spherical shape. When gold colloid has a uniform and perfect spherical shape, wine-red with high chroma saturation is exhibited. The gold colloid exhibiting such a color is most suitable for use in the in-vitro diagnostic agents. However, the color of gold colloid formed of particles having different aspect ratios exhibits violet-blue.
As described above, to increase the sensitivity of in-vitro diagnostic agents in accordance with various diagnostic purposes, gold colloid is desired to have a size suitable for use, a sharp particle size distribution and further a uniform and perfect spherical shape.
As a method for producing gold colloid, a method for reducing a gold salt solution is generally known. For example, Non-Patent Document 1 discloses a method for reducing gold chloride by sodium citrate trihydrate. Patent Documents 1 and 2 disclose methods of producing gold colloid by reducing a gold salt solution by a citrate or ascorbate.
Non-Patent Document 1: G. Frens, Nature Physical Science, 1973, Vol. 20, p. 241
Patent Document 1: Japanese Patent No. 2834400
Patent Document 2: Japanese Patent No. 2902954